CNX-2006

CNX-2006是不可逆的 EGFR 突变体抑制剂；对 EGFRT790M 的IC50 值小于20 nM。

研究领域 >> 癌症

EGFRT790M:20 nM (IC50)

EGFRL858R/T790M

与野生型EGFR细胞相比,CNX-2006抑制EGFR-T790M细胞生长高达1000倍。在暴露于药物1小时后,在含有T790M突变的细胞中观察到EGFR抑制,IC50值低于20nM。 CNX-2006还显着降低了源自H1975细胞的肿瘤球体积[1]。 CNX-2006表现出针对T790M的特异性和有效活性。该药物还显示出针对罕见EGFR突变的活性,包括G719S,L861Q,外显子19插入突变体(I744-K745insKIPVAI)和T854A,但不包括外显子20插入(H773-V774HVdup)。在体外抗性模型中,CNX-2006显着抑制抗性细胞的出现。长期接触不断增加剂量的CNX-2006无法选择和/或增强T790M介导的耐药性,使用PC-9或HCC827细胞(均含有外显子19缺失),或PC-9/ER和HCC827/ER细胞与现有T790M和对厄洛替尼的耐药性[2]。

[1]. Galvani E, et al. Abstract 3244: Role of epithelial-mesenchymal transition (EMT) in sensitivity to CNX-2006, a novel mutant-selective EGFR inhibitor which overcomes in vitro T790M-mediated resistance in NSCLC. CNX-2006, a novel mutant-selective EGFR inhibitor which overcomes in vitro T790M-mediated resistance in NSCLC. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Ishington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3244. doi:10.1158/1538-7445.AM2013-3244

[2]. Ohashi K, et al. Abstract 2101A: CNX-2006, a novel irreversible epidermal growth factor receptor (EGFR) inhibitor, selectively inhibits EGFR T790M and fails to induce T790M-mediated resistance in vitro. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Ishington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2101A. doi:10.1158/1538-7445.AM2013-2101A

奥斯替尼 | Tyrphostin B42 (AG-490) | 来那替尼 | 染料木素 | (-)-表没食子儿茶素没食子酸酯 | 4-(3-氯苯胺)-6,7-二甲氧基喹唑啉盐酸盐 | 达克替尼 | 图卡蒂尼(伊尔比尼替尼,ONT-380) | 波齐奥替尼(HM781-36B) | 奥莫替尼 | AZD 8931 | AZD-3759 | 吡咯替尼 | 卡纽替尼二盐酸盐 | (3R,4R)-4-氨基-1-[[4-[(3-甲氧基苯基)氨基]吡咯并[2,1-f][1,2,4]三嗪-5-基]甲基]哌啶-3-醇